We have established the colonies of LSL-Kras G12D (conditional K-ras mutant), LSL p53 R172 H (conditional p53 mutant), Pdx-1-Cre (pancreas-specific Cre-recombinase transgenic), and NOS2-, IL-6- and MIF-knockout mice. Inter-breeding of LSL-Kras G12D, p53 R172 H and Pdx-1-Cre generates the triple mutant mice that develop PDAC with a median survival of approximately 5 months and almost 100% mortality by 12 months. By cross-breeding these strains with NOS2 deficient mice, we have generated NOS2-deficient pancreatic cancer mouse model. Seven groups of these mice representing different genetic combinations have been set up to investigate the role of nitric oxide in the development and progression of pancreatic ductal adenocarcinoma. Similar strategy is being used to generate MIF- and IL-6 deficient pancreatic cancer mouse models.